Interaction between
Felbamate
and
Pexidartinib
Major
Synergy
Basic Information
| ID | DDInter715 and DDInter1435 |
| Interaction | Serious cases of hepatotoxicity, some fatal, have occurred in patients treated with pexidartinib. Concomitant use of other potentially hepatotoxic agents may potentiate the risk of liver injury. The mechanism of hepatotoxicity is unknown, its occurrence cannot be predicted, and it is unknown whether liver injury occurs in the absence of increased transaminases. |
| Management | The use of pexidartinib with other potentially hepatotoxic agents should be avoided. Patients treated with pexidartinib should have liver function tests, including AST, ALT, total bilirubin, direct bilirubin, ALP, and gamma-glutamyl transferase (GGT), prior to initiation of pexidartinib, weekly for the first 8 weeks, every 2 weeks for the next month, and every 3 months thereafter. Pexidartinib therapy may require a dosage reduction, to be withheld, or permanently discontinued based on the severity of the hepatotoxicity. A recurrence of increased serum transaminases, bilirubin, or ALP may occur upon rechallenge with a reduced dose of pexidartinib. Liver function tests should be performed weekly for the first month after rechallenge. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. |
| References | [1] "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc., Parsippany, NJ. [2] "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc., Parsippany, NJ. |
| Alternative for Felbamate |
N03A
|
| Alternative for Pexidartinib |
L01E
|
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.